Genes and the ageing muscle: a review on genetic association studies

Abstract

Western populations are living longer. Ageing decline in muscle mass and strength (i.e. sarcopenia) is becoming a growing public health problem, as it contributes to the decreased capacity for independent living. It is thus important to determine those genetic factors that interact with ageing and thus modulate functional capacity and skeletal muscle phenotypes in older people. It would be also clinically relevant to identify 'unfavourable' genotypes associated with accelerated sarcopenia. In this review, we summarized published information on the potential associations between some genetic polymorphisms and muscle phenotypes in older people. A special emphasis was placed on those candidate polymorphisms that have been more extensively studied, i.e. angiotensinconverting enzyme (ACE) gene I/D, α-actinin-3 (ACTN3) R577X, and myostatin (MSTN) K153R, among others. Although previous heritability studies have indicated that there is an important genetic contribution to individual variability in muscle phenotypes among old people, published data on specific gene variants are controversial. The ACTN3 R577X polymorphism could influence muscle function in old women, yet there is controversy with regards to which allele (R or X) might play a 'favourable' role. Though more research is needed, up-to-date MSTN genotype is possibly the strongest candidate to explain variance among muscle phenotypes in the elderly. Future studies should take into account the association between muscle phenotypes in this population and complex gene-gene and gene-environment interactions.

Association of the K153R polymorphism in the myostatin gene and extreme longevity

“…However, others have shown that myostatin expression does not increase (Kawada et al 2001;Welle et al 2002), and can even decrease (Baumann et al 2003), in ageing-induced sarcopenia in humans or rodents, thus questioning its involvement in muscle mass wasting during ageing. In fact, the R allele has not been associated with higher muscle mass/function in old Caucasian people (aged <80 years) (see Garatachea and Lucía (2013) for a review). Carriage of one R allele does not seem to exert a major influence in the muscle phenotypes of non-agenarians (Gonzalez-Freire et al 2010) whereas, surprisingly, the only two reported Caucasian old people with the RR genotype (i.e.…”

“…The Lys(K)153Arg(R) amino acid replacement is found within the active mature peptide of the myostatin protein; it could influence proteolytic processing with its pro-peptide or affinity to bind with the extracellular activin type II receptor (ActRIIB). The MSTN K153R polymorphism is thus a candidate to influence skeletal muscle phenotypes, included in old people (see Garatachea and Lucía (2013) for a recent review).…”

Genes expression profiles in the loin muscle of Manych Merino sheep with different live weight

“…At the same time, for regulatory genes, low expression indices may be enough for a major impact on the size and structure of the muscle (Braun & Gautel, 2011). We also based our choice of the studied genes on known data for farm animals about their impact on the quality of meat (Kogelman et al, 2011), and the information of the impact on muscle growth in humans and laboratory animals (Braun & Gautel, 2011;Garatachea & Lucía, 2013).…”

Associação de polimorfismos genéticos com capacidades físicas e composição corporal em idosas

“…ACTN3 is located in the Z-line inside muscle cells, where it helps to anchor actin filaments 9 . R577X polymorphism in the ACTN3 gene is classified as nonsense, in which there is an exchange of C à T nucleotide at position 1747 of the exon 16 , resulting in the exchange of the triplet of nucleotides responsible for the translation of arginine -then becoming a stop codon or triplet, generating a truncated protein. Individuals who have the XX genotype have lack of ACTN3, while heterozygotes (RX genotype) have fewer amount of ACTN3, but no disease 10 .…”

“…The elderly population is growing worldwide and also in Brazil, and there are very few surveys seeking to associate genetic variations in ACE and ACTN3 to physical fitness in the elderly [14][15] , especially in the Brazilian population [16][17] . Studies on this issue are primarily justified for showing the influence of genetics on physical fitness in the elderly in order to identify the loss of physical fitness before the individual gets old, which can harm ordinary activities of the daily living and provide data that can justify and contribute to future studies aimed at determining whether genetic polymorphisms may influence the magnitude of the response to interventions with exercise.…”